US5547995A - Use of Selegilene in veterinary medicine - Google Patents
Use of Selegilene in veterinary medicine Download PDFInfo
- Publication number
- US5547995A US5547995A US08/235,965 US23596594A US5547995A US 5547995 A US5547995 A US 5547995A US 23596594 A US23596594 A US 23596594A US 5547995 A US5547995 A US 5547995A
- Authority
- US
- United States
- Prior art keywords
- behavioral disorder
- selegiline
- anxiety
- behavioral
- disorders
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
Definitions
- present invention relates to the use of selegiline for the preparation of medicinal products useful for treating behavioral disorders with change of mood of pets, dogs and cats.
- Selegiline which is widely used in man in combination with levodopa in the treatment of parkinsonism, has also been studied in the treatment of diseases of ageing, such as Alzheimer's disease (cf. for example EP-A-0,406,488, -0,451,484).
- EP-A-0,473,252 It was recently described in EP-A-0,473,252 as being utilizable for retarding the damaging physiological effects of age on animals'bodies, in particular on the kidneys, the glands and the immune system and for limiting the deterioration of the learning and memorizing capacities of old cats and dogs; most of these activities, which can be observed only after a prolonged administration to the adult animals remain to be clinically demonstrated.
- Behavioral disorders with change of mood are characterized by a succession of phases of uncoordinated hyperactivity with insomnia, accompanied to a greater or lesser extent by aggressiveness and phases of apathy with difficulty in moving, by hypersomnia and hyporexia.
- Animals having such disorders are currently treated by administering to them neuroleptic drugs such as benzodiazepines or benzamides, whose efficacy, which appears only slowly, is often accompanied by a hypnotic activity.
- the invention relates to the use of selegiline, its racemate, the laevorotatory isomer or mixtures thereof in any proportions and pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of behavioral disorders with change of mood in dogs and cats.
- composition may be provided in one of the pharmaceutical forms generally used in veterinary medicine, preferably for oral administration.
- the daily dose of selegiline, HCl may range from 0.25 mg to 1 mg/kg of body weight of the animal and preferably close to 0.5 mg/kg; but these limits can be exceeded depending on the age of the animal or the intensity of the symptoms.
- the medicinal product can be provided orally in a form which can be easily divided, for example in the form of divisible tablets, into 2 or 4 pieces, manually. It will be generally administered orally in the morning on an empty stomach.
- the administration can be also performed subcutaneously, especially in cats, at the daily dose ranging from 0.25 to 4 mg/kg of selegiline, HCl.
- the treatment will be preferably maintained for a few days after the disappearance of the symptoms, however, it seems to be unnecessary to prolong it beyond 8 weeks; in general, it will last for 3 to 6 weeks.
- compositions conforming to the invention will be conventionally prepared with the excipients commonly used in the field in order to obtain solid, liquid or pasty compositions, especially tablets, hard gelatine capsules or powders; for example, tablets divisible into 4, containing 4 mg of selegiline, HCl per about 200 mg of excipient, will be recommended for animals of 2 to 8 kg whereas those comprising 10 mg of selegiline, HCl per 500 mg will be suitable for animals of 9 to 20 kg.
- aqueous solutions containing 10 mg of selegiline, HCl per ml will be used, the volume injected being from 0.5 to 2 ml according to the weight of the animal.
- the disturbed animal will steal items or will refuse to return them, will not respond to orders or to reprimand, will react badly, including with indifference, to changes and to oppressive situations.
- selegiline can be used in behavioral disorders with change of mood covering the following pathologies:
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the use of selegiline for preparing pharmaceutical compositions useful for treating behavioral disorders with change of mood in dogs and cats.
Description
present invention relates to the use of selegiline for the preparation of medicinal products useful for treating behavioral disorders with change of mood of pets, dogs and cats.
Selegiline, which is widely used in man in combination with levodopa in the treatment of parkinsonism, has also been studied in the treatment of diseases of ageing, such as Alzheimer's disease (cf. for example EP-A-0,406,488, -0,451,484).
It was recently described in EP-A-0,473,252 as being utilizable for retarding the damaging physiological effects of age on animals'bodies, in particular on the kidneys, the glands and the immune system and for limiting the deterioration of the learning and memorizing capacities of old cats and dogs; most of these activities, which can be observed only after a prolonged administration to the adult animals remain to be clinically demonstrated.
Other research scientists have observed in certain rats a substantial increase in life span when selegiline is regularly administered to them at the dose of 0.25 mg/kg after 23 months, whereas their average life span is 35 months; J. Knoll notes in Mechanisms of Ageing and Development 46 237-262 (1988) that this increase is accompanied by an improvement in the sexual activity of the animals and that these may be due to an action of selegiline on the dopaminergic neurons of the corpus striatum.
It has now been observed that the administration of selegiline to pets made it possible to improve very rapidly and to control in a few weeks their behaviour which is sometimes sufficiently intolerable for the owner to cause separation from his animal, euthanasia being frequently used at the present time.
Behavioral disorders with change of mood are characterized by a succession of phases of uncoordinated hyperactivity with insomnia, accompanied to a greater or lesser extent by aggressiveness and phases of apathy with difficulty in moving, by hypersomnia and hyporexia. Animals having such disorders are currently treated by administering to them neuroleptic drugs such as benzodiazepines or benzamides, whose efficacy, which appears only slowly, is often accompanied by a hypnotic activity.
Consequently, the invention relates to the use of selegiline, its racemate, the laevorotatory isomer or mixtures thereof in any proportions and pharmaceutically acceptable salts thereof for the preparation of a pharmaceutical composition for the treatment of behavioral disorders with change of mood in dogs and cats.
This composition may be provided in one of the pharmaceutical forms generally used in veterinary medicine, preferably for oral administration.
In this case, the daily dose of selegiline, HCl may range from 0.25 mg to 1 mg/kg of body weight of the animal and preferably close to 0.5 mg/kg; but these limits can be exceeded depending on the age of the animal or the intensity of the symptoms.
Since animals can be of very different weights, the medicinal product can be provided orally in a form which can be easily divided, for example in the form of divisible tablets, into 2 or 4 pieces, manually. It will be generally administered orally in the morning on an empty stomach.
The administration can be also performed subcutaneously, especially in cats, at the daily dose ranging from 0.25 to 4 mg/kg of selegiline, HCl.
The treatment will be preferably maintained for a few days after the disappearance of the symptoms, however, it seems to be unnecessary to prolong it beyond 8 weeks; in general, it will last for 3 to 6 weeks.
The pharmaceutical compositions conforming to the invention will be conventionally prepared with the excipients commonly used in the field in order to obtain solid, liquid or pasty compositions, especially tablets, hard gelatine capsules or powders; for example, tablets divisible into 4, containing 4 mg of selegiline, HCl per about 200 mg of excipient, will be recommended for animals of 2 to 8 kg whereas those comprising 10 mg of selegiline, HCl per 500 mg will be suitable for animals of 9 to 20 kg. For subcutaneous administration, aqueous solutions containing 10 mg of selegiline, HCl per ml will be used, the volume injected being from 0.5 to 2 ml according to the weight of the animal.
Reference can be made to manuals well known to galenists such as The theory and practice of Industrial Pharmacy--L. Lachman & al.--Lea & Febiger (1986)--Philadelphia, or Pharmacie gal enique A. Deno el, Fr. Jaminet.--Presses Universitaire de Li ege (1971).
1. Preliminary clinical study
In the following text, the clinical observations performed on dogs of various breeds, male or female, of more than 2 months old, whose behavioral disorders result in several symptoms in the following list are described:
bulimia with or without regurgitation and reingestion or, on the contrary, anorexia or dysorexia
eudipsia, polydipsia or lapping water without drinking
nibbling rituals or unusual licking
urinary or faecal filthiness
disrupted sleep
The disturbed animal will steal items or will refuse to return them, will not respond to orders or to reprimand, will react badly, including with indifference, to changes and to oppressive situations.
In table I below are summarized the conclusions of the observations for dogs to which tablets containing 10 mg of selegiline had been administered daily, in the morning on an empty stomach at the indicated dose.
TABLE I
______________________________________
Clinical Time required for
Animal Dose Observations cure
______________________________________
Dog No. 0.5 mg/kg An improvement in
Cure in 21 days
visible from the
first dose
Dog No. 2
0.5 mg/kg An improvement in
Cure in 21 days
visible from the
first dose
Dog No. 3
0.5 mg/kg An improvement is
Cure in 60 days
visible from the
first dose
Dog No. 4
0.5 mg/kg Improvement after
Care in 60 days
one week
Dog No. 5
0.25 mg/kg
The modifications
Improvement
are not very without cure
visible, the
filthiness in not
halted, no side
effects
Dog No. 6
0.25 mg/kg
The modifications
Improvement
are not very without cure
visible, the
filthiness in not
halted, no side
effects
______________________________________
From the clinical point of view, we observed disorders dominated by the production of disproportionate, frequent and prolonged emotional responses. These manifestations tend, in the case of those which have a voluntary expression to become uncontrolled and to progress to stereotypies. Thus, licking activities are observed, gradually losing their spontaneous interruption and result in a stereotyped licking which gradually invades the periods of wakefulness. The same applies to bulimias and potomanias, but includes aggressive responses with emotional components and the like. Sleep disorders corresponding to an advancing of paradoxical sleep resulting in sudden waking during the first 90 minutes of sleep and associated with phases of anxiety and agitation as bedtime approaches, are systematically observed in these animals. This precise typology led us to define a numerical scale for evaluation of the thymic state of the animals which we will call EEDD (Evaluation of the Emotional Disorders of Dogs) which will serve us as a tool for monitoring the treated animals and will permit a quantification of their cure.
EEDD≦20 normal animal
EEDD>20 animal suffering from behavioral disorders with change of mood.
The evaluation scale appended to the specification.
2. Clinical study
In Table II below are summarized the results of a study performed on 25 various pedigree dogs. The EEDD value was measured on the first day (D=0), 30th day (D=30) and 60 th day (D=60) of the treatment.
TABLE II
__________________________________________________________________________
ANIMAL EEDD
Name or Breed
Age D = 0
D = 30
D = 60
DIAGNOSIS
__________________________________________________________________________
Black Poodle
17 yrs
42 15 11 Dysthymia
Irish Setter
05 yrs
40 14 11 Dysthymia
Pinscher Crossbreed
06 yrs
37 22 20 Dysthymia
Poodle 07 yrs
26 14 14 Dysthymia
Alsatian 08 yrs
36 16 15 Involution depression
Cocker Spaniel
12 yrs
43 23 18 Aggressive, dominant
Sheepdog Crossbreed
2.5
yrs
39 23 -- Dominant + nibbling
stereotypy
Dark 0.5
yrs
24 24 13 Hyperactivity +
intermittent anxiety
Pinscher 01 yr 38 21 19 Hyperactivity +
hyperattachment
Labrador 10 mths
44 18 14 Hyperactivity
Pyrenean Sheepdog
03 yrs
43 19 18 Deprivation syndrome
Virgil 08 yrs
22 19 19 Separation anxiety
Christopher 06 yrs
25 18 -- Separation anxiety
Hatoll 01 yr 26 18 13 Separation anxiety
Libre 06 yrs
26 20 19 Overall anxiety
Elia 4.5
yrs
25 25 10 Overall anxiety
Honorine 1.5
yrs
22 21 15 Overall anxiety
Scarlett 05 yrs
21 22 15 Paroxystic anxiety
Pyrenean Mountain dog
05 yrs
30 24 18 Polyphobia - staggers
stereotypy
Leonberg 10 mths
24 21 18 Polyphobia + permanent
anxiety
Alsatian 03 yrs
22 22 15 Human phobia
Alsatian 02 yrs
24 20 Urban phobia +
sociopathy
Doberman 01 yr 22 17 16 Urban phobia +
intermittent anxiety
Sheepdog Crossbreed
05 yrs
30 32 17 Instrumental
sociopathy
Poodle 10 yrs
29 22 Instrumental
sociopathy + staggers
__________________________________________________________________________
This study demonstrates the effectiveness of the use of selegiline according to the present invention. The animals, practically without exception, reached, at the end of the treatment, an EEDD of less than 20, which characterizes a normal state.
Consequently, selegiline can be used in behavioral disorders with change of mood covering the following pathologies:
______________________________________
dysthymia intermittent anxiety
involution depression
paroxystic anxiety
aggressiveness via dominance
instrumental socio-
pathy
hyperactivity stereotypy (staggers/
leaking)
deprivation syndrome
phobia (human/urban)
separation anxiety socialization dis-
orders
______________________________________
__________________________________________________________________________
BEHAVIOUR
ITEM NOTE
__________________________________________________________________________
CENTRIPENTAL
Eating Bulimia 3
Anorexia/hyporexia 4
Dysorexia (passage from hyper to hypo)
5
Normal appetite 1
Bulimia with regurgitation and reingestion
3
Drinking Eudipsia 1
Polydipsia (documented)
5
Lapping water without drinking
3
Playing with the empty bowl
2
Habits Normal hygiene pattern
1
Licking, nibbling 4
Nibbling stereotypy, staggers
5
Sleep pattern
Normal (or no change)
1
Increase, hypersomnia
2
Insomnia during sleep
3
Wakes shortly after going to bed, sleep
5
anxiety
CENTRIFUGAL
Inquisitiveness
Normal 1
Simply inhibited 2
Increased and hypervigilance
4
Oral 5
Hides often 3
Aggression
Unchanged agressiveness (no relationship
1
problems)
Aggression from irritation
3
Aggression from fear 4
Aggression from fear and from irritation
5
Social Steals, does not release the stolen items
5
Relationships
Bites without growling
4
Not submissive 2
No self-control during play
2
Unchanged 1
Specific Same response capacity (taking
1
Relationships
fatigability into account)
Unpredictable response
3
No further response 5
Physical condition
Normal 1
Episodic tachycardia and/or tachypnoea
2
Diarrhoea, colic 2
Dyspepsia 2
Increased urination 3
Lick granuloma 4
Obesity 4
P.U.P.D. (poly urea/poly dypsia
4
TOTAL
__________________________________________________________________________
Claims (16)
1. A method for the treatment of a behavioral disorder with change of mood comprising administering to a mammal in need thereof selected from dogs and cats, an active ingredient selected from selegiline, its racemate, the laevorotatory isomer, mixtures thereof in any proportions and pharmaceutically acceptable salts thereof, in association with a pharmaceutically acceptable carrier.
2. The method of claim 1, wherein the active ingredient is selegiline HCl, the daily doses for oral administration ranging from 0.25 to 1 mg of selegiline, HCl per kg of body weight of the animal.
3. The method of claim 1, wherein the active ingredient is selegiline HCl, the daily doses for subcutaenous administration ranging from 0.25 to 4 mg of selegiline, HCl per kg of body weight of the animal.
4. The method of claim 1 wherein the behavioral disorder is dysthymia.
5. The method of claim 1 wherein the behavioral disorder is involution depression.
6. The method of claim 1 wherein the behavioral disorder is aggressiveness via dominance.
7. The method of claim 1 wherein the behavioral disorder is hyperactivity.
8. The method of claim 1 wherein the behavioral disorder is deprivation syndrome.
9. The method of claim 1 wherein the behavioral disorder is separation anxiety.
10. The method of claim 1 wherein the behavioral disorder is intermittent anxiety.
11. The method of claim 1 wherein the behavioral disorder is paroxystic anxiety.
12. The method of claim 1 wherein the behavioral disorder is instrumental sociopathy.
13. The method of claim 1 wherein the behavioral disorder is stereotypies.
14. The method of claim 1 wherein the behavioral disorder is phobia.
15. The method of claim 1 wherein the behavioral disorder is socialization disorders.
16. A method for the treatment of behavioral disorders with change of mood, said behavioral disorders being selected from dysthymia, involution depression, aggressiveness via dominance, hyperactivity, deprivation syndrome, separation anxiety, intermittent anxiety, paroxystic anxiety, instrumental sociopathy, stereotypies, phobia and socialization disorders, comprising administering to a mammal in need thereof selected from dogs and cats, an active ingredient selected from selegiline, its racemate, the laevorotatory isomer, mixtures thereof in any proportions and pharmaceutically acceptable salts thereof, in association with a pharmaceutically acceptable carrier.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9305305A FR2704756B1 (en) | 1993-05-04 | 1993-05-04 | Use of selegiline in veterinary medicine. |
| FR9305305 | 1993-05-04 | ||
| FR9315495A FR2713930B3 (en) | 1993-12-22 | 1993-12-22 | Use of Selegiline in veterinary medicine. |
| FR9315495 | 1993-12-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| US5547995A true US5547995A (en) | 1996-08-20 |
| US5547995B1 US5547995B1 (en) | 1998-01-27 |
Family
ID=26230300
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US08235965 Expired - Lifetime US5547995B1 (en) | 1993-05-04 | 1994-05-02 | Use of selegiline in veterinary medicine |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US5547995B1 (en) |
| EP (1) | EP0623344B1 (en) |
| AT (1) | ATE194911T1 (en) |
| CA (1) | CA2122780C (en) |
| DE (1) | DE69425345T2 (en) |
| DK (1) | DK0623344T3 (en) |
| ES (1) | ES2149850T3 (en) |
| GR (1) | GR3034661T3 (en) |
| PT (1) | PT623344E (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6221904B1 (en) | 1997-05-21 | 2001-04-24 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US6262111B1 (en) | 1997-05-21 | 2001-07-17 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US20030139443A1 (en) * | 2001-07-20 | 2003-07-24 | Bronk Brian Scott | Use of tachykinin antagonists, including NK-1 receptor antagonists, to modify unwanted behavior in dogs, cats and horses |
| US20050079205A1 (en) * | 2003-09-10 | 2005-04-14 | Miller Cheryl C. | Oleamide-containing composition for animal consumption |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2884421B1 (en) | 2005-04-15 | 2007-08-10 | Virbac Sa | NEW MEANS FOR CONTROLLING BEHAVIORAL DISORDERS IN PETS |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988004552A1 (en) * | 1986-12-19 | 1988-06-30 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Composition to prevent seasickness |
| WO1990001928A1 (en) * | 1988-08-17 | 1990-03-08 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Composition for the treatment of schizophrenia |
| WO1991018592A1 (en) * | 1990-05-25 | 1991-12-12 | Britannia Pharmaceuticals Limited | Pharmaceutical composition containing a lithium salt and an l-phenyl isopropylamine derivative for increasing the life expectancy |
| EP0473252A2 (en) * | 1990-08-31 | 1992-03-04 | Deprenyl Animal Health, Inc. | Use of L-deprenyl for retarding deterioration due to aging in dogs |
| WO1992017169A1 (en) * | 1991-04-04 | 1992-10-15 | The University Of Toronto Innovations Foundation | Use of deprenyl to maintain, prevent loss, or recover nerve cell function |
| US5169868A (en) * | 1991-03-01 | 1992-12-08 | University Of Saskatchewan | Aliphatic propargylamines as specific mao-b inhibitors |
| US5192808A (en) * | 1990-08-31 | 1993-03-09 | Deprenyl Animal Health, Inc. | Therapeutic effect of L-deprenyl in the management of pituitary-dependent hyperadrenocorticism (cushing's disease) |
-
1994
- 1994-05-02 AT AT94400949T patent/ATE194911T1/en not_active IP Right Cessation
- 1994-05-02 DE DE69425345T patent/DE69425345T2/en not_active Expired - Fee Related
- 1994-05-02 DK DK94400949T patent/DK0623344T3/en active
- 1994-05-02 US US08235965 patent/US5547995B1/en not_active Expired - Lifetime
- 1994-05-02 PT PT94400949T patent/PT623344E/en unknown
- 1994-05-02 EP EP94400949A patent/EP0623344B1/en not_active Expired - Lifetime
- 1994-05-02 ES ES94400949T patent/ES2149850T3/en not_active Expired - Lifetime
- 1994-05-03 CA CA002122780A patent/CA2122780C/en not_active Expired - Fee Related
-
2000
- 2000-10-23 GR GR20000402351T patent/GR3034661T3/en not_active IP Right Cessation
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1988004552A1 (en) * | 1986-12-19 | 1988-06-30 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Composition to prevent seasickness |
| WO1990001928A1 (en) * | 1988-08-17 | 1990-03-08 | Chinoin Gyógyszer és Vegyészeti Termékek Gyára Rt. | Composition for the treatment of schizophrenia |
| WO1991018592A1 (en) * | 1990-05-25 | 1991-12-12 | Britannia Pharmaceuticals Limited | Pharmaceutical composition containing a lithium salt and an l-phenyl isopropylamine derivative for increasing the life expectancy |
| EP0473252A2 (en) * | 1990-08-31 | 1992-03-04 | Deprenyl Animal Health, Inc. | Use of L-deprenyl for retarding deterioration due to aging in dogs |
| US5192808A (en) * | 1990-08-31 | 1993-03-09 | Deprenyl Animal Health, Inc. | Therapeutic effect of L-deprenyl in the management of pituitary-dependent hyperadrenocorticism (cushing's disease) |
| US5169868A (en) * | 1991-03-01 | 1992-12-08 | University Of Saskatchewan | Aliphatic propargylamines as specific mao-b inhibitors |
| WO1992017169A1 (en) * | 1991-04-04 | 1992-10-15 | The University Of Toronto Innovations Foundation | Use of deprenyl to maintain, prevent loss, or recover nerve cell function |
Non-Patent Citations (6)
| Title |
|---|
| E. Head et al., "Changes in Spontaneous Behavior in the Dog Following Oral Administration of L-Deprenyl", Chemical Abstracts, vol. 117, No. 25, Dec. 21, 1992, Abstract No. 245502c. |
| E. Head et al., Changes in Spontaneous Behavior in the Dog Following Oral Administration of L Deprenyl , Chemical Abstracts, vol. 117, No. 25, Dec. 21, 1992, Abstract No. 245502c. * |
| Goad et al, Biological Abstracts, vol. 92, No. 10, abstract #116325, 1991. |
| Goad et al, Biological Abstracts, vol. 92, No. 10, abstract 116325, 1991. * |
| Tariot et al., Biological Abstracts, vol. 84, No. 2, abstract #18676, 1987. |
| Tariot et al., Biological Abstracts, vol. 84, No. 2, abstract 18676, 1987. * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6221904B1 (en) | 1997-05-21 | 2001-04-24 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US6262111B1 (en) | 1997-05-21 | 2001-07-17 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US6420420B2 (en) | 1997-05-21 | 2002-07-16 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissue of a subject |
| US6608106B2 (en) | 1997-05-21 | 2003-08-19 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US20040002540A1 (en) * | 1997-05-21 | 2004-01-01 | Sloan-Kettering Institute For Cancer Research | Method for increasing the concentration of ascorbic acid in brain tissues of a subject |
| US20030139443A1 (en) * | 2001-07-20 | 2003-07-24 | Bronk Brian Scott | Use of tachykinin antagonists, including NK-1 receptor antagonists, to modify unwanted behavior in dogs, cats and horses |
| US20050079205A1 (en) * | 2003-09-10 | 2005-04-14 | Miller Cheryl C. | Oleamide-containing composition for animal consumption |
| EP1662895A1 (en) * | 2003-09-10 | 2006-06-07 | Hill's Pet Nutrition | Oleamide-containing composition for animal consumption |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2149850T3 (en) | 2000-11-16 |
| US5547995B1 (en) | 1998-01-27 |
| DE69425345T2 (en) | 2001-03-01 |
| CA2122780A1 (en) | 1994-11-05 |
| PT623344E (en) | 2000-12-29 |
| ATE194911T1 (en) | 2000-08-15 |
| EP0623344B1 (en) | 2000-07-26 |
| DE69425345D1 (en) | 2000-08-31 |
| DK0623344T3 (en) | 2000-12-18 |
| CA2122780C (en) | 2004-01-20 |
| GR3034661T3 (en) | 2001-01-31 |
| EP0623344A1 (en) | 1994-11-09 |
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